Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model

Kristin Hollister, Saritha Kusam, Hao Wu, Ninah Clegg, Arpita Mondal, Deepali V. Sawant, Alexander Dent

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Abstract

The transcriptional repressor Bcl6 controls development of the follicular Th cell (TFH) lineage, but the precise mechanisms by which Bcl6 regulates this process are unclear. A model has been proposed whereby Bcl6 represses the differentiation of T cells into alternative effector lineages, thus favoring TFH cell differentiation. Analysis of T cell differentiation using Bcl6-deficient mice has been complicated by the strong proinflammatory phenotype of Bcl6-deficient myeloid cells. In this study, we report data from a novel mouse model where Bcl6 is conditionally deleted in T cells (Bcl6fl/flCreCD4 mice). After immunization, programmed death-1 (PD-1)high TFH cells in Bcl6 fl/flCreCD4 mice are decreased >90% compared with control mice, and Ag-specific IgG is sharply reduced. Residual PD-1 highCXCR5+ TFH cells in Bcl6 fl/flCreCD4 mice show a significantly higher rate of apoptosis than do PD-1high CXCR5+ TFH cells in control mice. Immunization of Bcl6fl/flCreCD4 mice did not reveal enhanced differentiation into Th1, Th2, or Th17 lineages, although IL-10 expression by CD4 T cells was markedly elevated. Thus, T cell-extrinsic factors appear to promote the increased Th1, Th2, and Th17 responses in germline Bcl6-deficient mice. Furthermore, IL-10 may be a key target gene for Bcl6 in CD4 T cells, which enables Bcl6 to promote the TFH cell phenotype. Finally, our data reveal a novel mechanism for the role of Bcl6 in promoting TFH cell survival.

Original languageEnglish
Pages (from-to)3705-3711
Number of pages7
JournalJournal of Immunology
Volume191
Issue number7
DOIs
StatePublished - Oct 1 2013

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T-Lymphocytes
Interleukin-10
Cell Differentiation
Immunization
TCF Transcription Factors
Phenotype
Cell Lineage
Myeloid Cells
Cell Survival
Immunoglobulin G
Apoptosis
Genes

ASJC Scopus subject areas

  • Immunology

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Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model. / Hollister, Kristin; Kusam, Saritha; Wu, Hao; Clegg, Ninah; Mondal, Arpita; Sawant, Deepali V.; Dent, Alexander.

In: Journal of Immunology, Vol. 191, No. 7, 01.10.2013, p. 3705-3711.

Research output: Contribution to journalArticle

Hollister, Kristin ; Kusam, Saritha ; Wu, Hao ; Clegg, Ninah ; Mondal, Arpita ; Sawant, Deepali V. ; Dent, Alexander. / Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model. In: Journal of Immunology. 2013 ; Vol. 191, No. 7. pp. 3705-3711.
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